Insulin secretion in health and disease: Nutrients dictate the pace

Proceedings of the Nutrition Society

Volumn 75, Issue 1, 2016, Pages 19-29

  Regazzi, Romano ^a   Rodriguez Trejo, Adriana ^a   Jacovetti, Cécile ^a  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

Gene expression; Insulin; MicroRNA; Nutrients; cell

Indexed keywords

AMINO ACID; CHOLECYSTOKININ; EPIDERMAL GROWTH FACTOR; FATTY ACID; GASTRIC INHIBITORY POLYPEPTIDE; GASTRIN; GHRELIN; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 2; GLUCOSE; GLUCOSE TRANSPORTER; GROWTH HORMONE; GUANINE NUCLEOTIDE BINDING PROTEIN; INSULIN; MOTILIN; NEUROKININ A; NEUROKININ B; NEUROPEPTIDE; NEUROPEPTIDE Y; OBESTATIN; PEPTIDE YY; PLACENTA LACTOGEN; PROLACTIN; SECRETIN; SOMATOMEDIN C; SUBSTANCE P; TACHYKININ; UNTRANSLATED RNA; VASOACTIVE INTESTINAL POLYPEPTIDE;

CARBOHYDRATE METABOLISM; CELL ACTIVITY; CELL DIFFERENTIATION; CELL FUNCTION; CELL PROLIFERATION; CELL SIZE; CELL SURVIVAL; CONFERENCE PAPER; DIABETES MELLITUS; DIETARY INTAKE; GENE EXPRESSION; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; HUMAN; INSULIN RELEASE; INSULIN SYNTHESIS; LIPID DIET; LIPID METABOLISM; METABOLIC REGULATION; NONHUMAN; PANCREAS ISLET BETA CELL; PATHOGENESIS; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN RESTRICTION; RISK ASSESSMENT;

EID: 84959499990     PISSN: 00296651     EISSN: 14752719     Source Type: Journal    
DOI: 10.1017/S0029665115004152     Document Type: Conference Paper

References (125)

1. Huskisson E, Maggini S & Ruf M (2007) The role of vitamins and minerals in energy metabolism and well-being. J Int Med Res 35, 277-289.
2. Shenkin A (2006) The key role of micronutrients. Clin Nutr 25, 1-13.
3. Berthoud HR (2008) Vagal and hormonal gut-brain communication: from satiation to satisfaction. Neurogastroenterol Motil 20, Suppl. 1, 64-72.
4. Power ML & Schulkin J (2008) Anticipatory physiological regulation in feeDing biology: cephalic phase responses. Appetite 50, 194-206.
5. Giduck SA, Threatte RM & Kare MR (1987) Cephalic reflexes: their role in digestion and possible roles in absorption and metabolism. J Nutr 117, 1191-1196.
6. Teff KL (2011) How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiol Behav 103, 44-50.
7. Konturek SJ, Pepera J, Zabielski K et al. (2003) Brain-gut axis in pancreatic secretion and appetite control. J Physiol Pharmacol 54, 293-317.
8. Sanger GJ & Lee K (2008) Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders. Nat Rev Drug Discov 7, 241-254.
9. Stumvoll M (2004) Control of glycaemia: from molecules to men. Minkowski Lecture 2003. Diabetologia 47, 770-781.
10. Ferrannini E (2012) Physiology of glucose homeostasis and insulin therapy in type 1 and type 2 diabetes. Endocrinol Metab Clin North Am 41, 25-39.
11. Nolan CJ & Prentki M (2008) The islet beta-cell: fuel responsive and vulnerable. Trends Endocrinol Metab 19, 285-291.
12. Prentki M, Matschinsky FM & Madiraju SR (2013) Metabolic signaling in fuel-induced insulin secretion. Cell Metab 18, 162-185.
13. Newsholme P, Cruzat V, Arfuso F et al. (2014) Nutrient regulation of insulin secretion and action. J Endocrinol 221, R105-R120.
14. Gilon P, Ravier MA, Jonas JC et al. (2002) Control mechanisms of the oscillations of insulin secretion in vitro and in vivo. Diabetes 51, Suppl. 1, S144-S151.
15. Lefebvre PJ, Paolisso G, Scheen AJ et al. (1987). Pulsatility of insulin and glucagon release: physiological significance and pharmacological implications. Diabetologia 30, 443-452.
16. Zietek T & Daniel H (2015) Intestinal nutrient sensing and blood glucose control. Curr Opin Clin Nutr Metab Care 18, 381-388.
17. Thorens B (2011). Brain glucose sensing and neural regulation of insulin and glucagon secretion. Diab Obes Metab 13, Suppl. 1, 82-88.
18. Torres N, Noriega L & Tovar AR (2009) Nutrient modulation of insulin secretion. Vitam Horm 80, 217-244.
19. Teff K (2000) Nutritional implications of the cephalicphase reflexes: endocrine responses. Appetite 34, 206-213.
20. Powley TL & Berthoud HR (1985) Diet and cephalic phase insulin responses. Am J Clin Nutr 42, Suppl. 5, 991-1002.
21. Ahren B (2000) Autonomic regulation of islet hormone secretion-implications for health and disease. Diabetologia 43, 393-410.
22. Picard F, Naimi N, Richard D et al. (1999) Response of adipose tissue lipoprotein lipase to the cephalic phase of insulin secretion. Diabetes 48, 452-459.
23. Mitrakou A, Kelley D, Mokan M et al. (1992) Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. New Engl J Med 326, 22-29.
24. Calles-Escandon J & RobbinsDC (1987) Loss of early phase of insulin release in humans impairs glucose tolerance and blunts thermic effect of glucose. Diabetes 36, 1167-1172.
25. Teff KL & Townsend RR (1999) Early phase insulin infusion and muscarinic blockade in obese and lean subjects. Am J Physiol 277, 1 Pt 2, R198-R208.
26. Kraegen EW, Chisholm DJ & McNamara ME (1981) Timing of insulin delivery with meals. Horm Metab Res 13, 365-367.
27. Bruttomesso D, Pianta A, Mari A et al. (1999) Restoration of early rise in plasma insulin levels improves the glucose tolerance of type 2 diabetic patients. Diabetes 48, 99-105.
28. Schwartz MW, Seeley RJ, Tschop MH et al. (2013) Cooperation between brain and islet in glucose homeostasis and diabetes. Nature 503, 59-66.
29. Sala PC, Torrinhas RS, Giannella-Neto D et al. (2014) Relationship between gut hormones and glucose homeostasis after bariatric surgery. Diabetol Metab Syndr 6, 87
30. Perley MJ & Kipnis DM (1967) Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Investig 46, 1954-1962.
31. Ma J, Rayner CK, Jones KL et al. (2009) Insulin secretion in healthy subjects and patients with Type 2 diabetes-role of the gastrointestinal tract. Best Pract Res Clin Endocrinol Metab 23, 413-424.
32. Drucker DJ (2007) The role of gut hormones in glucose homeostasis. J Clin Investig 117, 24-32.
33. Alfa RW, Park S, Skelly KR et al. (2015) Suppression of insulin production and secretion by a decretin hormone. Cell Metab 21, 323-333.
34. Genton L & Kudsk KA (2003) Interactions between the enteric nervous system and the immune system: role of neuropeptides and nutrition. Am J Surg 186, 253-258.
35. Al Omran Y & Aziz Q (2014) The brain-gut axis in health and disease. Adv Exper Med Biol 817, 135-153.
36. Mayer EA (2011) Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 12, 453-466.
37. Rutter GA, Pullen TJ, Hodson DJ et al. (2015) Pancreatic beta-cell identity, glucose sensing and the control of insulin secretion. Biochem J 466, 203-218.
38. Donath MY, Storling J, Berchtold LA et al. (2008) Cytokines and beta-cell biology: from concept to clinical translation. Endocr Rev 29, 334-350.
39. Rutter GA & Hodson DJ (2013) Minireview: intraislet regulation of insulin secretion in humans. Mol Endocrinol 27, 1984-1995.
40. Eizirik DL, Korbutt GS & Hellerstrom C (1992) Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the beta-cell function. J Clin Investig 90, 1263-1268.
41. Davalli AM, RicorDi C, Socci C et al. (1991) Abnormal sensitivity to glucose of human islets cultured in a high glucose medium: partial reversibility after an additional culture in a normal glucose medium. J Clin Endocrinol Metab 72, 202-208.
42. Henquin JC (2011) The dual control of insulin secretion by glucose involves triggering and amplifying pathways in beta-cells. Diab Res Clin Pract 93, Suppl. 1, S27-S31.
43. Curry DL (1989) Effects of mannose and fructose on the synthesis and secretion of insulin. Pancreas 4, 2-9.
44. Sato Y, Ito T, Udaka N et al. (1996) Immunohistochemical localization of facilitated-diffusion glucose transporters in rat pancreatic islets. Tissue Cell 28, 637-643.
45. Kyriazis GA, Soundarapandian MM & Tyrberg B (2012) Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc Natl Acad Sci USA 109, E524-E532.
46. Henquin JC (2012) Do pancreatic beta cells taste nutrients to secrete insulin? Sci Signal 5, e36.
47. Malaisse WJ (2014) Insulin release: the receptor hypothesis. Diabetologia 57, 1287-1290.
48. Nolan CJ, Madiraju MS, Delghingaro-Augusto V et al. (2006) Fatty acid signaling in the beta-cell and insulin secretion. Diabetes 55, Suppl. 2, S16-S23.
49. Nolan CJ, Leahy JL, Delghingaro-Augusto V et al. (2006) Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling. Diabetologia 49, 2120-2130.
50. Prentki M & Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116, 1802-1812.
51. Esteves de Oliveira FC, Pinheiro Volp AC & Alfenas RC (2011) Impact of different protein sources in the glycemic and insulinemic responses. Nutr Hospital 26, 669-676.
52. Gannon MC, Ercan N, Westphal SA et al. (1993) Effect of added fat on plasma glucose and insulin response to ingested potato in individuals with NIDDM. Diab Care 16, 874-880.
53. Newsholme P, Bender K, Kiely A et al. (2007) Amino acid metabolism, insulin secretion and diabetes. Biochem Soc Trans 35, Pt 5, 1180-1186.
54. Bouwens L & Rooman I (2005) Regulation of pancreatic beta-cell mass. Physiol Rev 85, 1255-1270.
55. Oh YS (2015) Mechanistic insights into pancreatic beta-cell mass regulation by glucose and free fatty acids. Anat Cell Biol 48, 16-24.
56. Li M, Maddison LA, Page-McCaw P et al. (2014) Overnutrition induces beta-cell differentiation through prolonged activation of beta-cells in zebrafish larvae. Am J Physiol Endocrinol Metab 306, E799-E807.
57. Ninov N, Hesselson D, Gut P et al. (2013) Metabolic regulation of cellular plasticity in the pancreas. Curr Biol 23, 1242-1250.
58. Stolovich-Rain M, Enk J, Vikesa J et al. (2015) Weaning triggers a maturation step of pancreatic beta cells. Dev Cell 32, 535-545.
59. Porat S, Weinberg-Corem N, Tornovsky-Babaey S et al. (2011) Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab 13, 440-449.
60. Salpeter SJ, Klochendler A, Weinberg-Corem N et al. (2011) Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic beta-cells through glycolysis and calcium channels. Endocrinology 152, 2589-2598.
61. Dreja T, Jovanovic Z, Rasche A et al. (2010) Diet-induced gene expression of isolated pancreatic islets from a polygenic mouse model of the metabolic syndrome. Diabetologia 53, 309-320.
62. Roat R, Rao V, Doliba NM et al. (2014) Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57BL/6J mice. PLoS ONE 9, e86815.
63. Imai Y, Patel HR, Doliba NM et al. (2008) Analysis of gene expression in pancreatic islets from diet-induced obese mice. Physiol Genomics 36, 43-51.
64. Del Guerra S, Lupi R, Marselli L et al. (2005) Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 54, 727-735.
65. Hou JC, Williams D, Vicogne J et al. (2009) The glucose transporter 2 undergoes plasma membrane endocytosis and lysosomal degradation in a secretagogue-dependent manner. Endocrinology 150, 4056-4064.
66. Poitout V, Hagman D, Stein R et al. (2006) Regulation of the insulin gene by glucose and fatty acids. J Nutr 136, 873-876.
67. Hagman DK, Hays LB, Parazzoli SD et al. (2005) Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. J Biol Chem 280, 32413-32418.
68. Poitout V, Amyot J, Semache M et al. (2010) Glucolipotoxicity of the pancreatic beta cell. Biochim Biophys Acta 1801, 289-298.
69. Schwenk RW, Vogel H & Schurmann A (2013) Genetic and epigenetic control of metabolic health. Mol Metab 2, 337-347.
70. Hu Y, Xu XH, He K et al. (2014) Genome-wide analysis of DNA methylation variations caused by chronic glucolipotoxicity in beta-cells. Exp Clin Endocrinol Diab 122, 71-78.
71. Welters HJ & Kulkarni RN (2008) Wnt signaling: relevance to beta-cell biology and diabetes. Trends Endocrinol Metab 19, 349-355.
72. Pradas-Juni M, Nicod N, Fernandez-Rebollo E et al. (2014) Differential transcriptional and posttranslational transcription factor 7-like regulation among nondiabetic individuals and type 2 diabetic patients. Mol Endocrinol 28, 1558-1570.
73. Morrison F, Locke J, Arif M et al. (2013) Expression profiling of type 2 diabetes susceptibility genes in the pancreatic islets, adipose tissue and liver of obese mice. Exp Clin Endocrinol Diab 121, 413-419.
74. Hall E, Volkov P, Dayeh T et al. (2014) Effects of palmitate on genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets. BMCMed 12, 103.
75. Vaag A, Brons C, Gillberg L et al. (2014) Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes. Acta Obstet Gynecol Scand 93, 1099-1108.
76. Heerwagen MJ, Miller MR, Barbour LA et al. (2010) Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol 299, R711-R722.
77. Howie GJ, Sloboda DM, Kamal T et al. (2009) Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol 587, Pt 4, 905-915.
78. Howie GJ, Sloboda DM, Reynolds CM et al. (2013) Timing of maternal exposure to a high fat diet and development of obesity and hyperinsulinemia in male rat offspring: same metabolic phenotype, different developmental pathways? J Nutr Metab 2013, 517384.
79. Reusens B, Sparre T, Kalbe L et al. (2008) The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation. Diabetologia 51, 836-845.
80. Sandovici I, Smith NH, Nitert MD et al. (2011) Maternal diet and aging alter the epigenetic control of a promoterenhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc. Natl Acad Sci USA 108, 5449-5454.
81. Kapoor RR, Locke J, Colclough K et al. (2008) Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. Diabetes 57, 1659-1663.
82. Pearson ER, Boj SF, Steele AM et al. (2007) Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 4, e118.
83. Ng SF, Lin RC, Laybutt DR et al. (2010) Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467, 963-966.
84. Ng SF, Lin RC, Maloney CA et al. (2014) Paternal high-fat diet consumption induces common changes in the transcriptomes of retroperitoneal adipose and pancreatic islet tissues in female rat offspring. FASEB J 28, 1830-1841.
85. Ost A, Lempradl A, Casas E et al. (2014) Paternal diet defines offspring chromatin state and intergenerational obesity. Cell 159, 1352-1364.
86. Rando OJ & Simmons RA (2015) I'm eating for two: parental dietary effects on offspring metabolism. Cell 161, 93-105.
87. International Human Genome Sequencing C (2004) Finishing the euchromatic sequence of the human genome. Nature 431, 931-945.
88. Genomes Project C, Abecasis GR, Altshuler D et al. (2010) A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073.
89. Naqvi AR, Islam MN, Choudhury NR et al. (2009) The fascinating world of RNA interference. Int J Biol Sci 5, 97-117.
90. Dozmorov MG, Giles CB, Koelsch KA et al. (2013) Systematic classification of non-coDing RNAs by epigenomic similarity. BMC Bioinf 14, Suppl. 14, S2.
91. Siomi MC, Sato K, Pezic D et al. (2011) PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol 12, 246-258.
92. Grivna ST, Beyret E, Wang Z et al. (2006) A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 20, 1709-1714.
93. Dumortier O, Hinault C & Van Obberghen E (2013) MicroRNAs and metabolism crosstalk in energy homeostasis. Cell Metab 18, 312-324.
94. Esguerra JL, Mollet IG, Salunkhe VA et al. (2014) Regulation of pancreatic beta cell stimulus-secretion coupling by microRNAs. Genes (Basel) 5, 1018-1031.
95. Guay C, Roggli E, Nesca V et al. (2011) Diabetes mellitus, a microRNA-related disease? Transl Res 157, 253-264.
96. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233.
97. Wilusz JE, Sunwoo H & Spector DL (2009) Long noncoDing RNAs: functional surprises from the RNA world. Genes Dev 23, 1494-1504.
98. Ulitsky I & Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154, 26-46.
99. Lovis P, Roggli E, Laybutt DR et al. (2008) Alterations in microRNA expression contribute to fatty acid-induced pancreatic beta-cell dysfunction. Diabetes 57, 2728-2736.
100. Tang X, Muniappan L, Tang G et al. (2009) Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription. RNA 15, 287-293.
101. Zhao X, Mohan R, Ozcan S et al. (2012) MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic beta-cells. J Biol Chem 287, 31155-31164.
102. El Ouaamari A, Baroukh N, Martens GA et al. (2008) miR-375 targets 3?-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes 57, 2708-2717.
103. Poy MN, Eliasson L, Krutzfeldt J et al. (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230.
104. Poy MN, Hausser J, Trajkovski M et al. (2009) miR-375 maintains normal pancreatic alpha-and beta-cell mass. Proc Natl Acad Sci USA 106, 5813-5818.
105. Fred RG, Bang-Berthelsen CH, Mandrup-Poulsen T et al. (2010) High glucose suppresses human islet insulin biosynthesis by inducing miR-133a leaDing to decreased polypyrimidine tract binDing protein-expression. PLoS ONE 5, e10843.
106. Bagge A, Clausen TR, Larsen S et al. (2012) MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion. Biochem Biophys Res Commun 426, 266-272.
107. Pullen TJ, da Silva Xavier G, Kelsey G et al. (2011) miR-29a and miR-29b contribute to pancreatic beta-cell-specific silencing of monocarboxylate transporter 1 (Mct1). Mol Cell Biol 31, 3182-3194.
108. Esguerra JL, Bolmeson C, Cilio CM et al. (2011) Differential glucose-regulation of microRNAs in pancreatic islets of non-obese type 2 diabetes model Goto-Kakizaki rat. PLoS ONE 6, e18613.
109. Nesca V, Guay C, Jacovetti C et al. (2013) Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes. Diabetologia 56, 2203-2212.
110. Tattikota SG, Rathjen T, McAnulty SJ et al. (2014) Argonaute2 mediates compensatory expansion of the pancreatic beta cell. Cell Metab 19, 122-134.
111. Jacovetti C, Abderrahmani A, Parnaud G et al. (2012) MicroRNAs contribute to compensatory beta cell expansion during pregnancy and obesity. J Clin Invest 122, 3541-3551.
112. Jacovetti C, Jimenez V, Ayuso E et al. (2015) Contribution of intronic miR-338-3p and its hosting gene AATK to compensatory beta-cell mass expansion. Mol Endocrinol 29, 693-702.
113. Locke JM, da Silva Xavier G, Dawe HR et al. (2014) Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion. Diabetologia 57, 122-128.
114. Latreille M, Hausser J, Stutzer I et al. (2014) MicroRNA-7a regulates pancreatic beta cell function. J Clin Invest 124, 2722-2735.
115. Kameswaran V, Bramswig NC, McKenna LB et al. (2014) Epigenetic regulation of theDLK1-MEG3 microRNAcluster in human type 2 diabetic islets. Cell Metab 19, 135-145.
116. Belgardt BF, Ahmed K, Spranger M et al. (2015) The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes. Nat Med 21, 619-627.
117. Zhao E, Keller MP, Rabaglia ME et al. (2009) Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice. Mamm Genome 20, 476-485.
118. Dumortier O, Hinault C, Gautier N et al. (2014) Maternal protein restriction leads to pancreatic failure in offspring: role of misexpressed microRNA-375. Diabetes 63, 3416-3427.
119. Jacovetti C, Matkovich SJ, Rodriguez-Trejo A et al. (2015) Postnatal beta-cell maturation is associated with islet-specific microRNA changes induced by nutrient shifts at weaning. Nat Commun 6, 8084.
120. Castell-Auvi A, Cedo L, Movassat J et al. (2013) Procyanidins modulate microRNA expression in pancreatic islets. J Agric Food Chem 61, 355-363.
121. Kornfeld JW & Bruning JC (2014) Regulation of metabolism by long, non-coDing RNAs. Front Genet 5, 57.
122. Knoll M, Lodish HF & Sun L (2015) Long non-coDing RNAs as regulators of the endocrine system. Nat Rev Endocrinol 11, 151-160.
123. Moran I, Akerman I, van de Bunt M et al. (2012) Human beta cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in Type 2 diabetes. CellMetab 16, 435-448.
124. Fadista J, Vikman P, Laakso EO et al. (2014) Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism. Proc Natl Acad Sci USA 111, 13924-13929.
125. Ding GL, Wang FF, Shu J et al. (2012) Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes 61, 1133-1142.